ArticleCell communication and signaling : CCS2022
Inhibition of AKT induces p53/SIRT6/PARP1-dependent parthanatos to suppress tumor growth.
Article in Cell communication and signaling : CCS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- Cellular senescence and regulated cell death in cancer: mechanisms, cross-regulatory networks and therapeutic implications.Journal of hematology & oncology · 2026Review
- Ketogenic diet, cardiometabolic diseases and aging.Journal of geriatric cardiology : JGC · 2026Article
- Curcumin induces and enhances the PARP1-mediated parthanatos in diffuse large B cell lymphoma.Oncology letters · 2026Article
- Biobank of genetically defined murine prostate cancer tumoroids uncovers oncogenic pathways and drug vulnerabilities driven by PTEN-loss.Cell reports methods · 2026Article
- Leveraging Deep Learning to Construct a Programmed Cell Death-Driven Prognostic Signature in Acute Myeloid Leukemia.Current issues in molecular biology · 2026Article
- Propofol regulates METTL3-mediated PARP-1 mScientific reports · 2026Article
- LncRNA OTUD6B-AS1 overexpression induces parthanatos in esophageal adenocarcinoma cells by binding to miR-145-5p and promoting AIF expression.American journal of translational research · 2026Article
- Identification and Experimental Verification Reveal SLC2A3 Associated With Prognosis and Immune Infiltration in Colon Adenocarcinoma.Mediators of inflammation · 2026Article
- SIRT6 in Cancer: Mechanistic Insights into Its Dual Roles in Cancer Biology and Implications for Precision Therapeutic Development.Biomolecules · 2025Review
- Uncovering the Mechanism of Quercetin in the Treatment of Premature Ovarian Failure: A Multi-Faceted Approach Integrating Network Pharmacology, Bioinformatics Analysis and Experimental Validation.Food science & nutrition · 2025Article
- p53-regulated non-apoptotic cell death pathways and their relevance in cancer and other diseases.Nature reviews. Molecular cell biology · 2025Review
- Parthanatos and apoptosis: unraveling their roles in cancer cell death and therapy resistance.EXCLI journal · 2025Review
- Advances in non-apoptotic regulated cell death: implications for malignant tumor treatment.Frontiers in oncology · 2025Review
- Multi-omics analysis of parthanatos related molecular subgroup and prognostic model development in stomach adenocarcinoma.PloS one · 2025Article
- Temporal transcriptomic atlas reveals sequential engagement of classical and emerging regulated cell death pathways during PRRSV infection.Frontiers in veterinary science · 2025Article
- Titanium Dioxide Nanoparticles Induce Cell Cycle Arrest and Apoptosis through Inhibiting PI3K/AKT/mTOR Pathway in Spermatogonia.Biological trace element research · 2024Article
- Research advances on silence information regulator 6 as a potential therapeutic target for bone regeneration and repair.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- Oxidative cell death in cancer: mechanisms and therapeutic opportunities.Cell death & disease · 2024Review
- N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma.Cancer research communications · 2024Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTargeting AKT suppresses tumor growth through inducing apoptosis, however, during which whether other forms of cell death occurring is poorly understood.
methodsThe effects of increasing PARP1 dependent cell death (parthanatos) induced by inhibiting AKT on cell proliferation were determined by CCK-8 assay, colony formation assay, Hoechst 33,258 staining and analysis of apoptotic cells by flow cytometry. For the detailed mechanisms during this process, Western blot analysis, qRT-PCR analysis, immunofluorescence and co-immunoprecipitation were performed. Moreover, the inhibition of tumor growth by inducing p53/SIRT6/PARP1-dependent parthanatos was further verified in the xenograft mouse model.
resultsFor the first time, we identified that inhibiting AKT triggered parthanatos, a new form of regulated cell death, leading to colon cancer growth suppression. For the mechanism investigation, we found that after pharmacological or genetic AKT inhibition, p53 interacted with SIRT6 and PARP1 directly to activate it, and promoted the formation of PAR polymer. Subsequently, PAR polymer transported to outer membrane of mitochondria and resulted in AIF releasing and translocating to nucleus thus promoting cell death. While, blocking PARP1 activity significantly rescued colon cancer from death. Furthermore, p53 deletion or mutation eliminated PAR polymer formation, AIF translocation, and PARP1 dependent cell death, which was promoted by overexpression of SIRT6. Meanwhile, reactive oxygen species production was elevated after inhibition of AKT, which might also play a role in the occurrence of parthanatos. In addition, inhibiting AKT initiated protective autophagy simultaneously, which advanced tumor survival and growth.
conclusionOur findings demonstrated that AKT inhibition induced p53-SIRT6-PARP1 complex formation and the activation of parthanatos, which can be recognized as a novel potential therapeutic strategy for cancer. Video Abstract.
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